PMID- 31749124 OWN - NLM STAT- MEDLINE DCOM- 20210603 LR - 20220210 IS - 1936-0568 (Electronic) IS - 1936-055X (Print) IS - 1936-055X (Linking) VI - 14 IP - 3 DP - 2020 Sep TI - Tumor Infiltrating Lymphocytes and CD8+ T Cell Subsets as Prognostic Markers in Patients with Surgically Treated Laryngeal Squamous Cell Carcinoma. PG - 689-700 LID - 10.1007/s12105-019-01101-6 [doi] AB - To evaluate the prognostic significance of tumor infiltrating lymphocytes (TILs) and of CD8+ T-cell subsets in patients with surgically treated laryngeal squamous cell carcinoma (LSCC), LSCC from 283 patients were examined. TIL density was morphologically assessed on whole sections. CD8+ cell counts/mm(2) were evaluated on multiple tissue microarray cores per tumor (median counts for high/low CD8+/mm(2)). TIL density and CD8+ counts weakly correlated with each other (Spearman's rho = 0.348). Heterogeneous CD8+ counts/mm(2) were demonstrated in 28% of the tumors. In univariate analysis, a significant interaction was observed between CD8 expression and nodal status with respect to outcome; in node-positive patients, those with high CD8+ tumors had 77% lower risk of relapse (interaction p < 0.001) and 74% lower risk for death (interaction p = 0.002) compared to patients with low CD8+ tumors. In multivariate analysis, higher TIL density independently conferred lower risk for relapse in the entire cohort (HR 0.87; 95% CI 0.77-0.98; Wald's p = 0.017) and in node-positive patients (HR 0.41; 95% CI 0.23-0.75; p = 0.003) and, similarly, for death (p = 0.025 and p = 0.003, respectively). High CD8+ was not a significant independent prognostic marker in any analysis setting. The assessment of CD8+ infiltrates does not seem to offer additional prognostic information over the morphologically assessed TIL density. It also appears that the favorable prognostic impact of higher TIL density and CD8+ infiltrates mostly concerns node-positive but not node-negative disease. If validated in larger node-positive cohorts, these findings are worth considering for the diagnostic development of immune cell infiltrates in LSCC. FAU - Chatzopoulos, Kyriakos AU - Chatzopoulos K AUID- ORCID: 0000-0001-6769-6952 AD - Laboratory of Molecular Oncology, School of Medicine, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, University Campus, 54124, Thessaloniki, Greece. chatzopouloskyr@gmail.com. AD - Division of Anatomic Pathology, Mayo Clinic, 200 1st Street SW, Rochester, MN, 55905, USA. chatzopouloskyr@gmail.com. FAU - Kotoula, Vassiliki AU - Kotoula V AD - Laboratory of Molecular Oncology, School of Medicine, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, University Campus, 54124, Thessaloniki, Greece. AD - Department of Pathology, School of Health Sciences, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece. FAU - Manoussou, Kyriaki AU - Manoussou K AD - Section of Biostatistics, Hellenic Cooperative Oncology Group, Data Office, Athens, Greece. FAU - Markou, Konstantinos AU - Markou K AD - First Department of Otorhinolaryngology, School of Health Sciences, Faculty of Medicine, AHEPA Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece. FAU - Vlachtsis, Konstantinos AU - Vlachtsis K AD - First Department of Otorhinolaryngology, School of Health Sciences, Faculty of Medicine, AHEPA Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece. FAU - Angouridakis, Nikolaos AU - Angouridakis N AD - First Department of Otorhinolaryngology, School of Health Sciences, Faculty of Medicine, AHEPA Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece. FAU - Nikolaou, Angelos AU - Nikolaou A AD - ENT Department, G. Papanikolaou General Hospital, Thessaloniki, Greece. FAU - Vassilakopoulou, Maria AU - Vassilakopoulou M AD - Department of Pathology, Yale University School of Medicine, New Haven, CT, USA. FAU - Psyrri, Amanda AU - Psyrri A AD - Division of Oncology, Second Department of Internal Medicine, Attikon University Hospital, Athens, Greece. FAU - Fountzilas, Georgios AU - Fountzilas G AD - Laboratory of Molecular Oncology, School of Medicine, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, University Campus, 54124, Thessaloniki, Greece. AD - Aristotle University of Thessaloniki, Thessaloniki, Greece. LA - eng GR - Research Grant HE R_5G/Ellenike Synergazomene Onkologike Omada/ PT - Journal Article DEP - 20191120 PL - United States TA - Head Neck Pathol JT - Head and neck pathology JID - 101304010 RN - 0 (Biomarkers, Tumor) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Biomarkers, Tumor/*immunology MH - CD8-Positive T-Lymphocytes/*immunology MH - Female MH - Humans MH - Laryngeal Neoplasms/*immunology/surgery MH - Lymphocytes, Tumor-Infiltrating/*immunology MH - Male MH - Middle Aged MH - Prognosis MH - Squamous Cell Carcinoma of Head and Neck/*immunology/surgery PMC - PMC7413976 OTO - NOTNLM OT - CD8 OT - Head and neck cancer OT - TILs OT - Tumor-infiltrating lymphocytes COIS- Amanda Psyrri discloses-Consultation fees: Amgen, Merck Serono, Roche, BMS, AstraZeneca, MSD. Honoraria: Amgen, Merck Serono, Roche, BMS, AstraZenecea, MSD. Research funds: BMS, Kura. Georgios Fountzilas discloses-Advisory Board of Pfizer, Sanofi and Roche. Honoraria from AstraZeneca. The other authors have no conflicts of interest to disclose. EDAT- 2019/11/22 06:00 MHDA- 2021/06/04 06:00 PMCR- 2020/11/20 CRDT- 2019/11/22 06:00 PHST- 2019/08/07 00:00 [received] PHST- 2019/11/15 00:00 [accepted] PHST- 2019/11/22 06:00 [pubmed] PHST- 2021/06/04 06:00 [medline] PHST- 2019/11/22 06:00 [entrez] PHST- 2020/11/20 00:00 [pmc-release] AID - 10.1007/s12105-019-01101-6 [pii] AID - 1101 [pii] AID - 10.1007/s12105-019-01101-6 [doi] PST - ppublish SO - Head Neck Pathol. 2020 Sep;14(3):689-700. doi: 10.1007/s12105-019-01101-6. Epub 2019 Nov 20.